Isolation, identification and immunosuppressive activity of SDZ-IMM-125
metabolites from human liver microsomes.
Dieden R, Verbeeck RK, Latinne D, Wallemacq P, Maton N, Lhoest GJ
Department of Pharmaceutical Sciences-UCL, Pharmacokinetics and Metabolism
Unit-FATC Laboratory of Mass Spectrometry, Brussels, Belgium.
SDZ-IMM-125 N-methyl leucine 9 hydroxylated in the gamma position is
a metabolite which was extracted from incubated human liver microsomes
and subsequently separated by normal and reverse-phase HPLC. This metabolite
was identified by fast atom bombardment mass spectrometry, electrospray-ms/ms
mass spectrometry and nuclear magnetic resonance spectroscopy. The in vitro
50% inhibitory concentration, tested against bidirectional mixed lymphocyte
reaction was 80 microg/l indicating that this metabolite does not retain
in vitro immunosuppressive activity most probably due to the structural
modification of SDZ-IMM-125 in the recognized binding region to cyclophilin
A reducing its binding affinity relative to the parent drug.
PMID: 10412896, UI: 99339241